Improving zero-mode waveguide structure for enhancing signal-to-noise ratio of real-time single-molecule fluorescence imaging: A computational study

AbstractNanopores bear great potential as single-molecule tools for bioanalytical sensing and sequencing, due to their exceptional sensing capabilities, high-throughput, and low cost. The detection principle relies on detecting small differences in the ionic current as biomolecules traverse the nanopore. A major bottleneck for the further progress of this technology is the noise that is present in the ionic current recordings, because it limits the signal-to-noise ratio and thereby the effective time resolution of the experiment. Here, we review the main types of noise at low and high frequencies and discuss the underlying physics. Moreover, we compare biological and solid-state nanopores in terms of the signal-to-noise ratio (SNR), the important figure of merit, by measuring free translocations of a short ssDNA through a selected set of nanopores under typical experimental conditions. We find that SiNx solid-state nanopores provide the highest SNR, due to the large currents at which they can be operated and the relatively low noise at high frequencies. However, the real game-changer for many applications is a controlled slowdown of the translocation speed, which for MspA was shown to increase the SNR >160-fold. Finally, we discuss practical approaches for lowering the noise for optimal experimental performance and further development of the nanopore technology.

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Novel optical design for improved signal to noise ratio of a real time M-squared measurement

International Congress on Applications of Lasers & Electro-Optics ◽

10.2351/1.5118543 ◽

2016 ◽

Author(s):

Michael Scaggs

Keyword(s):

Real Time ◽

Signal To Noise Ratio ◽

Optical Design ◽

Signal To Noise ◽

Noise Ratio

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Development and Characterization of an Electrocochleography-Guided Robotics-Assisted Cochlear Implant Array Insertion System

Otolaryngology ◽

10.1177/01945998211049210 ◽

2021 ◽

pp. 019459982110492

Author(s):

Allan M. Henslee ◽

Christopher R. Kaufmann ◽

Matt D. Andrick ◽

Parker T. Reineke ◽

Viral D. Tejani ◽

...

Keyword(s):

Cochlear Implant ◽

Real Time ◽

Signal To Noise Ratio ◽

Electrode Array ◽

High Signal ◽

Animal Testing ◽

Signal To Noise ◽

Noise Ratio ◽

Hearing Outcomes

Objective Electrocochleography (ECochG) is increasingly being used during cochlear implant (CI) surgery to detect and mitigate insertion-related intracochlear trauma, where a drop in ECochG signal has been shown to correlate with a decline in hearing outcomes. In this study, an ECochG-guided robotics-assisted CI insertion system was developed and characterized that provides controlled and consistent electrode array insertions while monitoring and adapting to real-time ECochG signals. Study Design Experimental research. Setting A research laboratory and animal testing facility. Methods A proof-of-concept benchtop study evaluated the ability of the system to detect simulated ECochG signal changes and robotically adapt the insertion. Additionally, the ECochG-guided insertion system was evaluated in a pilot in vivo sheep study to characterize the signal-to-noise ratio and amplitude of ECochG recordings during robotics-assisted insertions. The system comprises an electrode array insertion drive unit, an extracochlear recording electrode module, and a control console that interfaces with both components and the surgeon. Results The system exhibited a microvolt signal resolution and a response time <100 milliseconds after signal change detection, indicating that the system can detect changes and respond faster than a human. Additionally, animal results demonstrated that the system was capable of recording ECochG signals with a high signal-to-noise ratio and sufficient amplitude. Conclusion An ECochG-guided robotics-assisted CI insertion system can detect real-time drops in ECochG signals during electrode array insertions and immediately alter the insertion motion. The system may provide a surgeon the means to monitor and reduce CI insertion–related trauma beyond manual insertion techniques for improved CI hearing outcomes.

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